Figure 2
From: Ponatinib sensitizes myeloma cells to MEK inhibition in the high-risk VQ model
Ponatinib, but not other TKIs, synergizes with trametinib in vitro. (A) Relative viability results for tyrosine kinase inhibitors (TKIs) from AOD IX panel at 100 nM and 1000 nM concentration alone or in the presence of 10 nM trametinib, as in Fig. 1A. (B) Screening results of TKIs as single agents and with 10 nM trametinib. Trametinib and Ponatinib are highlighted as in (A). Of note, 10 nM trametinib yielded ~ 50% viability relative to DMSO control. (C–E) VQ 4935 and 4938 cells were treated with the indicated concentrations of two compounds for 48 h. Relative viability to DMSO treated control was then measured using the CellTiter-Glo assay. (C) Dose–response results for ponatinib against VQ 4935 and 4938 cell lines. IC50 values were calculated by logistic regression using the GraphPad Prism software. (D) Selected viability results for combination treatment of trametinib (Tra) and ponatinib (Pon) against VQ 4935 and 4938 cells. (E) ZIP synergy plots of Tra and Pon in VQ 4935 and 4938 cells. Zip Synergy scores were generated using the SynergyFinder online tool.
